CCI-779 and Rituximab in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00109967
First received: May 3, 2005
Last updated: March 21, 2014
Last verified: December 2013
Results First Received: December 3, 2013  
Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Recurrent Mantle Cell Lymphoma
Interventions: Biological: rituximab
Drug: temsirolimus

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Seventy-one patients seen at 35 sites were enrolled on this trial between May 6, 2005 and March 6, 2009. Two patients canceled before receiving treatment and 69 patients were therefore included in the analysis. There were 48 patients in group 1 (rituximab-sensitive) and 21 (rituximab-refractory) in group 2.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The patients were stratified by their previous response to rituximab into rituximab sensitive (group 1) or rituximab refractory (group 2) groups. Rituximab refractory was defined as no response (stable disease or progression) or a response that lasted <6 months the last time the patient received rituximab alone or rituximab with chemotherapy.

Reporting Groups
  Description
Group I: Rituximab Sensitive

Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment.

rituximab: 375 mg/m^2 Given IV

temsirolimus: 25 mg given IV

Group II: Rituximab Refractory

Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment.

rituximab: 375 mg/m^2 Given IV

temsirolimus: 25 mg given IV


Participant Flow:   Overall Study
    Group I: Rituximab Sensitive     Group II: Rituximab Refractory  
STARTED     50     21  
COMPLETED     30     15  
NOT COMPLETED     20     6  
Cancel Prior to Treatment                 2                 0  
Adverse Event                 12                 1  
Withdrawal by Subject                 5                 0  
Physician Decision                 1                 3  
Death                 0                 2  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Group I: Rituximab Sensitive

Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment.

rituximab: 375 mg/m^2 Given IV temsirolimus: 25 mg given IV

Group II: Rituximab Refractory

Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment.

rituximab: 375 mg/m^2 Given IV temsirolimus: 25 mg given IV

Total Total of all reporting groups

Baseline Measures
    Group I: Rituximab Sensitive     Group II: Rituximab Refractory     Total  
Number of Participants  
[units: participants]
  48     21     69  
Age  
[units: years]
Median ( Full Range )
  67.5  
  ( 51 to 86 )  
  66  
  ( 44 to 85 )  
  67  
  ( 44 to 86 )  
Gender  
[units: participants]
     
Female     13     6     19  
Male     35     15     50  
Region of Enrollment  
[units: participants]
     
United States     48     21     69  



  Outcome Measures
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1.  Primary:   Overall Response Rate (Complete and Partial Responses) as Defined by the International Workshop Criteria   [ Time Frame: Up to 12, 28-day cycles. ]

2.  Secondary:   Time to Progression   [ Time Frame: Patients were followed up to five years after registration. ]

3.  Secondary:   Duration of Response   [ Time Frame: Response duration is followed up to 5 years from registration. ]

4.  Secondary:   Toxicity   [ Time Frame: Assessed during treatment (up to 12, 28-day cycles) ]

5.  Secondary:   Overall Survival   [ Time Frame: Patients were followed for survival status for up to 5 years. ]


  Serious Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

Reporting Groups
  Description
Group I: Rituximab Sensitive temsirolimus: 25 mg given IV
Group II: Rituximab Refractory temsirolimus: 25 mg given IV

Serious Adverse Events
    Group I: Rituximab Sensitive     Group II: Rituximab Refractory  
Total, serious adverse events      
# participants affected / at risk     16/48 (33.33%)     7/21 (33.33%)  
Blood and lymphatic system disorders      
Febrile neutropenia † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
Hemoglobin decreased † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
Cardiac disorders      
Left ventricular failure † 1    
# participants affected / at risk     0/48 (0.00%)     1/21 (4.76%)  
# events     0     1  
Myocardial ischemia † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
Gastrointestinal disorders      
Abdominal pain † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
Hemorrhoids † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
Rectal pain † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
General disorders      
Death NOS † 1    
# participants affected / at risk     0/48 (0.00%)     1/21 (4.76%)  
# events     0     1  
Disease progression † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
Fever † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
Localized edema † 1    
# participants affected / at risk     0/48 (0.00%)     1/21 (4.76%)  
# events     0     1  
Immune system disorders      
Hypersensitivity † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
Infections and infestations      
Catheter related infection † 1    
# participants affected / at risk     2/48 (4.17%)     0/21 (0.00%)  
# events     2     0  
Pneumonia † 1    
# participants affected / at risk     4/48 (8.33%)     1/21 (4.76%)  
# events     4     1  
Skin infection † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
Soft tissue infection † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
Investigations      
Aspartate aminotransferase increased † 1    
# participants affected / at risk     0/48 (0.00%)     1/21 (4.76%)  
# events     0     1  
Leukocyte count decreased † 1    
# participants affected / at risk     0/48 (0.00%)     1/21 (4.76%)  
# events     0     1  
Neutrophil count decreased † 1    
# participants affected / at risk     3/48 (6.25%)     1/21 (4.76%)  
# events     5     1  
Platelet count decreased † 1    
# participants affected / at risk     3/48 (6.25%)     2/21 (9.52%)  
# events     5     2  
Metabolism and nutrition disorders      
Dehydration † 1    
# participants affected / at risk     0/48 (0.00%)     1/21 (4.76%)  
# events     0     1  
Serum calcium decreased † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
Nervous system disorders      
Encephalopathy † 1    
# participants affected / at risk     0/48 (0.00%)     1/21 (4.76%)  
# events     0     1  
Peripheral sensory neuropathy † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
Tremor † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
Renal and urinary disorders      
Renal failure † 1    
# participants affected / at risk     0/48 (0.00%)     2/21 (9.52%)  
# events     0     2  
Respiratory, thoracic and mediastinal disorders      
Dyspnea † 1    
# participants affected / at risk     1/48 (2.08%)     1/21 (4.76%)  
# events     3     1  
Hypoxia † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
Pleural effusion † 1    
# participants affected / at risk     0/48 (0.00%)     1/21 (4.76%)  
# events     0     1  
Pneumonitis † 1    
# participants affected / at risk     4/48 (8.33%)     1/21 (4.76%)  
# events     5     1  
Vascular disorders      
Hematoma † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
Hemorrhage † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
Thrombosis † 1    
# participants affected / at risk     1/48 (2.08%)     0/21 (0.00%)  
# events     1     0  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 6




  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Stephen M. Ansell, M.D., Ph.D.
Organization: Mayo Clinic
e-mail: ansell.stephen@mayo.edu


No publications provided by National Cancer Institute (NCI)

Publications automatically indexed to this study:

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00109967     History of Changes
Other Study ID Numbers: NCI-2009-00644, N038H, U10CA025224, CDR0000425334
Study First Received: May 3, 2005
Results First Received: December 3, 2013
Last Updated: March 21, 2014
Health Authority: United States: Food and Drug Administration